Hemodynamics

Assessment of the hemodynamic effects of nitrous oxide in humans is often complicated by concomitant administration of volatile anesthetics, opioids, or other anesthetic adjuvants in the presence or absence of cardiovascular disease. Typical clinical concentrations of nitrous oxide (e.g., 40% to 70%) cause modest increases in heart rate in healthy volunteers.^{[461] [483]} Small increases in heart rate also occur when hyperbaric concentrations of nitrous oxide are administered^[484] or when this anesthetic gas is added to volatile anesthetics.^[485] Declines in heart rate have been observed with nitrous oxide in patients with coronary artery disease anesthetized with isoflurane^[194] or halothane.^[486] Modest reductions in heart rate have been also reported in patients anesthetized with morphine or fentanyl undergoing cardiac surgery.^{[465] [470] [471]} Sixty-percent nitrous oxide causes small increases in arterial pressure in humans.^[483] Increases in arterial pressure also occur under hyperbaric conditions^[484] or during halothane anesthesia in volunteers,^{[457] [467]} consistent with a mild sympathomimetic effect. Other studies have also indicated that partial substitution of nitrous oxide for a volatile anesthetic does not affect or modestly increases arterial pressure during enflurane,^[472] isoflurane,^[469] or desflurane^[180] anesthesia in experiments conducted at a constant MAC. In contrast, reductions in arterial pressure have been observed in patients with coronary artery disease receiving nitrous oxide in the presence and absence of opioids.^{[470] [476] [487]}

Small increases in cardiac output and stroke volume have been observed during administration of 60% nitrous oxide in oxygen in volunteers.^[483] However, cardiac output remains unchanged in the presence of hyperbaric nitrous oxide.^[484] Cardiac output is greater in volunteers anesthetized with halothane and nitrous oxide than in those receiving halothane alone, ^[467] concomitant with increases in sympathetic nervous system tone. The addition of nitrous oxide to enflurane, isoflurane, or desflurane anesthesia also modestly increased cardiac output.^{[37] [38] [469] [472]} In contrast, nitrous oxide reduces cardiac output and stroke volume in healthy volunteers ^[488] and patients with cardiac disease receiving opioids.^{[465] [470] [471] [486] [487]} Hyperbaric nitrous oxide (1.5 MAC) caused a modest reduction in systemic vascular resistance.^[484] In contrast, systemic vascular resistance is higher during volatile anesthesia in the presence compared with the absence of nitrous oxide.^{[37] [38] [467] [469] [472]} Pretreatment with the ganglionic blocker hexamethonium attenuated the relative increase in systemic vascular resistance observed during administration of halothane and nitrous oxide,^[457] findings that may be consistent with a reduction in sympathetic nervous system tone. Nitrous oxide-induced increases in systemic vascular resistance have also been reported in volunteers and patients with cardiac disease anesthetized with opioids.^{[465] [488] [489]}

Nitrous oxide increases venous tone and decreases venous capacitance in conscious volunteers.^[461] This anesthetic gas also modestly increases pulmonary artery pressures and pulmonary vascular resistance in patients with coronary artery disease anesthetized with morphine and diazepam ^[470] or halothane.^[490] The combined effects of enhanced venous return, elevated pulmonary vascular resistance, and depressed contractile function probably contribute to the increases in central venous pressure observed with nitrous oxide in humans. Hyperbaric nitrous oxide also enhances central venous pressure in association with increases in pulmonary vascular resistance.^[484] Nitrous oxide inhibits norepinephrine uptake by the lung, and subsequent increases in plasma norepinephrine levels detected in the pulmonary vasculature may be partially responsible for the characteristic increases in pulmonary vascular resistance observed during administration of this agent.^[491] Nitrous oxide-induced increases in pulmonary vascular resistance may be more pronounced in adults with pulmonary hypertension^{[490] [492]} and children with increased pulmonary blood flow.^[493] Elevations in pulmonary artery pressures and vascular resistance have also been described during administration of nitrous oxide in neonatal lambs.^[494] Such increases in pulmonary vascular resistance may adversely enhance right-to-left atrial or ventricular shunts and compromise arterial oxygenation in patients with congenital heart disease.^[495]